Haemophilus influenzae lipopolysaccharide-induced blood brain barrier permeability during experimental meningitis in the rat

• Published in: The Journal of clinical investigation Vol. 82; no. 4; pp. 1339 - 1346
• Main Authors: WISPELWEY, B, LESSE, A. J, HANSEN, E. J, SCHELD, W. M
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01-10-1988
• Subjects: Animals; Bacterial diseases; Bacterial Vaccines - toxicity; Biological and medical sciences; Blood-Brain Barrier - drug effects; Capillary Permeability - drug effects; Dose-Response Relationship, Drug; Experimental bacterial diseases and models; Haemophilus influenzae; Haemophilus influenzae - analysis; Infectious diseases; Kinetics; Leukopenia - physiopathology; Lipopolysaccharides - toxicity; Medical sciences; Meningitis - etiology; Meningitis - physiopathology; Rats; Rats, Inbred Strains; Nervous system diseases; Biochemical analysis; Rat; Rodentia; Cytology; Cerebrospinal fluid; Permeability; Blood brain barrier; Haemophilus influenzae; Infection; Pasteurellaceae; Vertebrata; Experimental disease; Mammalia; Bacteriosis; Lipopolysaccharide; Bacteria; Meningitis
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI113736

The factors responsible for blood-brain barrier (BBB) injury during bacterial meningitis are incompletely defined. We evaluated the role of Haemophilus influenzae type b (Hib) lipopolysaccharide (LPS) in the alteration of blood-brain barrier permeability (BBBP) in an adult, normal and leukopenic, rat model of meningitis. Intracisternal inoculation of Hib LPS resulted in (a) dose-dependent increases in BBBP from 2 pg to 20 ng, with significant attenuation in the peak response after challenge with 500 ng and 1 microgram; (b) time-dependent increases in BBBP, with a delayed onset of at least 2 h, maximum alteration at 4 h, and complete reversal at 18 h; (c) greater BBBP than after challenge with the live parent strain; (d) and a close correlation (r = 0.86) between CSF pleocytosis and BBBP at 4 h. The LPS effect was significantly inhibited by preincubation with Polymyxin B and neutrophil acyloxyacyl hydrolase, however two different oligosaccharide-specific monoclonal antibodies did not inhibit activity. No change in BBBP after inoculation with Hib LPS occurred in leukopenic rats. Hib LPS, in the setting of an intact leukocyte response, exerts profound effects on BBBP.